The use of bisphosphonate and testosterone in young people with Duchenne muscular dystrophy: an international clinician survey

Sarah McCarrison; Shima Abdelrahman; Justin H. Davies; Talat Mushtaq; Raja Padidela; Vrinda Saraff; Claire L. Wood; Sze Choong Wong

doi:10.1515/jpem-2025-0039

Article

The use of bisphosphonate and testosterone in young people with Duchenne muscular dystrophy: an international clinician survey

Sarah McCarrison , Shima Abdelrahman , Justin H. Davies , Talat Mushtaq , Raja Padidela , Vrinda Saraff , Claire L. Wood and Sze Choong Wong

Published/Copyright: April 25, 2025

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information Explore this Subject

From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 8

Abstract

Objectives

Delayed puberty and osteoporosis are significant challenges in boys with Duchenne muscular dystrophy (DMD). The current International Care Considerations for DMD recommend bisphosphonate after first fracture and testosterone for delayed puberty from 12 years. This study aimed to investigate the current clinical practices of clinicians managing osteoporosis and testosterone treatment in DMD.

Methods

An online survey was circulated to paediatric clinicians involved in the management of bone health and puberty in DMD via patient groups (UK, USA, Italy, Israel).

Results

A total of 51/105 (48 %) responses were received. For osteoporosis, vertebral fracture of any grade (86 %) and long bone fracture (67 %) were the most common indications for starting bisphosphonates, with IV zoledronate being the most used agent (86 %). Approaches varied in managing bisphosphonate side effects, and transitioning care to adult specialists. Opinions differed on starting bisphosphonate before fracture. Fourty-nine clinicians managing pubertal disorders reported initiating testosterone for delayed puberty typically between 12 and 14 years, with majority prescribing intramuscular injections (96 %). Duration of testosterone therapy varied, with some using short-term courses and others continuing until adulthood.

Conclusions

This international survey highlights variability in the management of osteoporosis and delayed puberty in DMD. Recommendations on management of side-effects of IV bisphosphonate, osteoporosis therapy during transition, and longer-term treatment into adulthood is required. There is a need for further guidance on testosterone therapy, particularly in regard to monitoring after discontinuation and the threshold for re-initiation of treatment.

Keywords: Duchenne muscular dystrophy; osteoporosis; bisphosphonate; testosterone; delayed puberty

Corresponding author: Dr. Sze Choong Wong, Bone, Endocrine & Nutrition Research Group in Glasgow, Human Nutrition, University of Glasgow, Glasgow, UK; and Department of Paediatric Endocrinology, Royal Hospital for Children, 1345 Govan Road, Glasgow, G51 4TF, UK, E-mail: jarod.wong@glasgow.ac.uk

Research ethics: Not applicable.
Informed consent: Not applicable.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: SCW: Consultancy – Santhera, Roche, Novartis; Speaker’s honorarium – Nutricia, Sandoz, Novonordisk, Roche. All other authors state no conflict of interest.
Research funding: SA is funded by Muscular Dystrophy UK, Action Duchenne and Duchenne Parent Project Netherlands. CW is funded by an NIHR advanced fellowship. The funders had no role in the design, data collection, data analysis, and reporting of this study.
Data availability: All data generated or analysed during this study are included in this article and its supplementary material files. Further enquiries can be directed to the corresponding author.

References

1. Bez Batti Angulski, A, Hosny, N, Cohen, H, Martin, AA, Hahn, D, Bauer, J, et al.. Duchenne muscular dystrophy: disease mechanism and therapeutic strategies. Front Physiol 2023;14. https://doi.org/10.3389/fphys.2023.1183101.Search in Google Scholar PubMed PubMed Central

2. Joseph, S, Wang, C, Bushby, K, Guglieri, M, Horrocks, I, Straub, V, et al.. Fractures and linear growth in a nationwide cohort of boys with Duchenne muscular dystrophy with and without glucocorticoid treatment: results from the UK NorthStar database. JAMA Neurol 2019;76:701–9. https://doi.org/10.1001/jamaneurol.2019.0242.Search in Google Scholar PubMed PubMed Central

3. Crabtree, NJ, Adams, JE, Padidela, R, Shaw, NJ, Högler, W, Roper, H, et al.. Growth, bone health & ambulatory status of boys with DMD treated with daily vs. intermittent oral glucocorticoid regimen. Bone 2018;116:181–6. https://doi.org/10.1016/j.bone.2018.07.019.Search in Google Scholar PubMed

4. Birnkrant, DJ, Bushby, K, Bann, CM, Alman, BA, Apkon, SD, Blackwell, A, et al.. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol 2018;17:347–61. https://doi.org/10.1016/s1474-4422(18)30025-5.Search in Google Scholar

5. Bushby, K, Finkel, R, Birnkrant, DJ, Case, LE, Clemens, PR, Cripe, L, et al.. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol 2010;9:177–89. https://doi.org/10.1016/s1474-4422(09)70272-8.Search in Google Scholar

6. McCarrison, S, Denker, M, Dunne, J, Horrocks, I, McNeilly, J, Joseph, S, et al.. Frequency of delayed puberty in boys with contemporary management of Duchenne muscular dystrophy. J Clin Res Pediatr Endocrinol 2024;16:458–65. https://doi.org/10.4274/jcrpe.galenos.2024.2024-2-18.Search in Google Scholar PubMed PubMed Central

7. Birnkrant, DJ, Bushby, K, Bann, CM, Apkon, SD, Blackwell, A, Brumbaugh, D, et al.. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol 2018;17:251–67. https://doi.org/10.1016/s1474-4422(18)30024-3.Search in Google Scholar

8. Henderson, A, Harley, G, Horrocks, I, Joseph, S, Dunne, J, Pysden, K, et al.. Endocrine and bone monitoring in boys with Duchenne muscular dystrophy; do we adhere to the standards of care? J Neuromuscul Dis 2023;10:1143–4. https://doi.org/10.3233/jnd-230144.Search in Google Scholar PubMed PubMed Central

9. Galetaki, D, Szymczuk, V, Shi, M, Merchant, N. Is endocrine surveillance important in the care of Duchenne Muscular Dystrophy? Results from a national survey to patients and families on endocrine complications. eNeurologicalSci 2024;36:100513. https://doi.org/10.1016/j.ensci.2024.100513.Search in Google Scholar PubMed PubMed Central

10. Phung, K, Crabtree, N, Connolly, AM, Furlong, P, Hoffman, EP, Jackowski, SA, et al.. Moving beyond the 2018 minimum international care considerations for osteoporosis management in Duchenne muscular dystrophy (DMD): meeting report from the 3rd international muscle-bone interactions meeting 7th and 14th november 2022. J Neuromuscul Dis 2024;11:233–52. https://doi.org/10.3233/jnd-230176.Search in Google Scholar

11. Phung, K, McAdam, L, Ma, J, McMillan, HJ, Jackowski, S, Scharke, M, et al.. Risk factors associated with incident vertebral fractures in steroid-treated males with Duchenne muscular dystrophy. J Clin Endocrinol Metab 2024;109:536–48. https://doi.org/10.1210/clinem/dgad435.Search in Google Scholar PubMed

12. Ward, LM, Choudhury, A, Alos, N, Cabral, DA, Rodd, C, Sbrocchi, AM, et al.. Zoledronic acid vs placebo in pediatric glucocorticoid-induced osteoporosis: a randomized, double-blind, phase 3 trial. J Clin Endocrinol Metab 2021;106:e5222–35. https://doi.org/10.1210/clinem/dgab458.Search in Google Scholar PubMed

13. Sbrocchi, AM, Rauch, F, Jacob, P, McCormick, A, McMillan, HJ, Matzinger, MA, et al.. The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. Osteoporos Int 2012;23:2703–11. https://doi.org/10.1007/s00198-012-1911-3.Search in Google Scholar PubMed

14. Misof, BM, Roschger, P, McMillan, HJ, Ma, J, Klaushofer, K, Rauch, F, et al.. Histomorphometry and bone matrix mineralization before and after bisphosphonate treatment in boys with Duchenne muscular dystrophy: a paired transiliac biopsy study. J Bone Min Res 2016;31:1060–9. https://doi.org/10.1002/jbmr.2756.Search in Google Scholar PubMed

15. Lim, A, Zacharin, M, Pitkin, J, de Valle, K, Ryan, MM, Simm, PJ. Therapeutic options to improve bone health outcomes in Duchenne muscular dystrophy: zoledronic acid and pubertal induction. J Paediatr Child Health 2017;53:1247–8. https://doi.org/10.1111/jpc.13692.Search in Google Scholar PubMed

16. Ronsley, R, Islam, N, Kang, M, Nadel, H, Reilly, C, Metzger, D, et al.. Effects of bisphosphonate therapy on bone mineral density in boys with Duchenne muscular dystrophy. Clin Med Insights Endocrinol Diabetes 2020;13. https://doi.org/10.1177/1179551420972400.Search in Google Scholar PubMed PubMed Central

17. Zheng, WB, Dai, Y, Hu, J, Zhao, DC, Wang, O, Jiang, Y, et al.. Effects of bisphosphonates on osteoporosis induced by Duchenne muscular dystrophy: a prospective study. Endocr Pract 2020;26:1477–85. https://doi.org/10.4158/ep-2020-0073.Search in Google Scholar

18. Zacharin, M, Lim, A, Gryllakis, J, Siafarikas, A, Jefferies, C, Briody, J, et al.. Randomized controlled trial evaluating the use of zoledronic acid in Duchenne muscular dystrophy. J Clin Endocrinol Metab 2021;106:2328–42. https://doi.org/10.1210/clinem/dgab302.Search in Google Scholar PubMed

19. Ward, LM, Denker, AE, Porras, A, Shugarts, S, Kline, W, Travers, R, et al.. Single-dose pharmacokinetics and tolerability of alendronate 35- and 70-milligram tablets in children and adolescents with osteogenesis imperfecta type I. J Clin Endocrinol Metab 2005;90:4051–6. https://doi.org/10.1210/jc.2004-2054.Search in Google Scholar PubMed

20. Ward, LM, Rauch, F. Oral bisphosphonates for paediatric osteogenesis imperfecta? Lancet 2013;382:1388–9. https://doi.org/10.1016/s0140-6736(13)61531-7.Search in Google Scholar PubMed

21. Tian, C, Wong, BL, Hornung, L, Khoury, JC, Rybalsky, I, Shellenbarger, KC, et al.. Oral bisphosphonate treatment in patients with Duchenne muscular dystrophy on long term glucocorticoid therapy. Neuromuscul Disord 2020;30:599–610. https://doi.org/10.1016/j.nmd.2020.06.005.Search in Google Scholar PubMed

22. Kumaki, D, Nakamura, Y, Sakai, N, Kosho, T, Nakamura, A, Hirabayashi, S, et al.. Efficacy of denosumab for glucocorticoid-induced osteoporosis in an adolescent patient with Duchenne muscular dystrophy: a case report. JBJS Case Connect 2018;8:e22. https://doi.org/10.2106/jbjs.cc.17.00190.Search in Google Scholar PubMed

23. Hung, C, Mathews, KD, Shibli-Rahhal, A. Effect of denosumab on bone health in adult patients with duchenne/becker muscular dystrophy: a report of 2 cases. JBJS Case Connect 2022;12. https://doi.org/10.2106/jbjs.cc.21.00664.Search in Google Scholar

24. Nasomyont, N, Keefe, C, Tian, C, Hornung, L, Khoury, J, Tilden, JC, et al.. Safety and efficacy of teriparatide treatment for severe osteoporosis in patients with Duchenne muscular dystrophy. Osteoporos Int 2020;31:2449–59. https://doi.org/10.1007/s00198-020-05549-z.Search in Google Scholar PubMed

25. Catalano, A, Vita, GL, Russo, M, Vita, G, Lasco, A, Morabito, N, et al.. Effects of teriparatide on bone mineral density and quality of life in Duchenne muscular dystrophy related osteoporosis: a case report. Osteoporos Int 2016;27:3655–9. https://doi.org/10.1007/s00198-016-3761-x.Search in Google Scholar PubMed

26. Choong Wong, S, Joseph, S, Capaldi, N, Marco, MD, Dunne, J, Guglieri, M, et al.. A survey of the feasibility of developing osteoporosis clinical trials in Duchenne muscular dystrophy: survey of the opinion of young people with Duchenne muscular dystrophy, families and clinicians. Clin Trials 2021;18:39–50. https://doi.org/10.1177/1740774520958395.Search in Google Scholar PubMed

27. Chodankar, D. Introduction to real-world evidence studies. Perspect Clin Res 2021;12:171–4. https://doi.org/10.4103/picr.picr_62_21.Search in Google Scholar PubMed PubMed Central

28. Wood, CL, Hollingsworth, KG, Hughes, E, Punniyakodi, S, Muni-Lofra, R, Mayhew, A, et al.. Pubertal induction in adolescents with DMD is associated with high satisfaction, gonadotropin release and increased muscle contractile surface area. Eur J Endocrinol 2021;184:67–79. https://doi.org/10.1530/eje-20-0709.Search in Google Scholar PubMed

29. Lee, SL, Lim, A, Munns, C, Simm, PJ, Zacharin, M. Effect of testosterone treatment for delayed puberty in Duchenne muscular dystrophy. Horm Res Paediatr 2020;93:108–18. https://doi.org/10.1159/000508290.Search in Google Scholar PubMed

30. Loscalzo, E, See, J, Bharill, S, Yousefzadeh, N, Gough, E, Wu, M, et al.. Growth hormone and testosterone delay vertebral fractures in boys with muscular dystrophy on chronic glucocorticoids. Osteoporos Int 2024;35:327–38. https://doi.org/10.1007/s00198-023-06951-z.Search in Google Scholar PubMed PubMed Central

31. Lucas-Herald, AK, Mason, E, Beaumont, P, Mason, A, Shaikh, MG, Wong, SC, et al.. Single-centre experience of testosterone therapy for boys with hypogonadism. Horm Res Paediatr 2018;90:123–7. https://doi.org/10.1159/000490738.Search in Google Scholar PubMed

32. Wood, CL, Hollingsworth, KG, Bokaie, E, Hughes, E, Muni-Lofra, R, Mayhew, A, et al.. Is ongoing testosterone required after pubertal induction in Duchenne muscular dystrophy? Endocr Connect 2023;12. https://doi.org/10.1530/ec-23-0245.Search in Google Scholar

Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/jpem-2025-0039).

Received: 2025-01-18

Accepted: 2025-04-14

Published Online: 2025-04-25

Published in Print: 2025-08-26

You are currently not able to access this content.

Supplementary Material

Articles in the same Issue

https://doi.org/10.1515/jpem-2025-0039

Keywords for this article

Duchenne muscular dystrophy; osteoporosis; bisphosphonate; testosterone; delayed puberty